Neuronal signalling of zinc: from detection and modulation to function

Zinc is an essential trace element that stabilizes protein structures and allosterically modulates a plethora of enzymes, ion channels and neurotransmitter receptors. Labile zinc (Zn²⁺) acts as an intracellular and intercellular signalling molecule in response to various stimuli, which is especially important in the central nervous system. Zincergic neurons, characterized by Zn²⁺ deposits in synaptic vesicles and presynaptic Zn²⁺ release, are found in the cortex, hippocampus, amygdala, olfactory bulb and spinal cord. To provide an overview of synaptic Zn²⁺ and intracellular Zn²⁺ signalling in neurons, the present paper summarizes the fluorescent sensors used to detect Zn²⁺ signals, the cellular mechanisms regulating the generation and buffering of Zn²⁺ signals, as well as the current perspectives on their pleiotropic effects on phosphorylation signalling, synapse formation, synaptic plasticity, as well as sensory and cognitive function.